Pro-haemorrhagic effects of calcium antagonists: a comparison of isradipine and atenolol on ex vivo platelet function in hypertensive subjects.
It has been suggested that long term treatment with calcium antagonist drugs might inhibit platelet function and lead to an anti-atheromatous effect. However recent data have also suggested that such an effect might increase mortality due to an increased incidence of gastrointestinal bleeding. We identified 43 subjects from general practice with uncomplicated mild to moderate hypertension to compare the effects of the calcium antagonist isradipine with that of the beta-blocker atenolol on platelet function, plasma beta-thromboglobulin levels, fibrinolysis, and serum lipids in a randomised double-blind parallel group study. After careful evaluation to exclude concomitant aspirin use, only 24 subjects were eligible to enter the study. While isradipine and atenolol produced comparable and clinically significant falls in blood pressure (167 +/- 2/102 +/- 1 to 153 +/- 3/91 +/- 2 mm Hg, and 165 +/- 2/101 +/- 1 to 156 +/- 4/91 +/- 2 mm Hg, respectively), neither drug produced a detectable effect on ex vivo platelet aggregation, platelet retention, or thromboxane generation with adrenaline, collagen, adenosine-di-phosphate, or platelet activating factor. However a decrease in plasma beta-thromboglobulin levels was observed which reached statistical significance (P < 0.05) after 12 weeks treatment in the isradipine but not the atenolol group. A 39% reduction with isradipine compared with 34% following atenolol treatment. Euglobulin clot lysis time was not altered by either drug. Serum cholesterol concentrations were also unaltered by drug treatment. Therapeutic doses of the calcium antagonist isradipine may produce a minor indirect effect on platelet function after several weeks of treatment. However, this is of doubtful clinical importance and may simply reflect an effect of lowered blood pressure on platelet function.
Smith
A
A
Discipline of Clinical Pharmacology, Faculty of Medicine and Health Sciences, University of Newcastle, NSW, Australia.
McPherson
J
J
Taylor
M
M
Mason
A
A
Carney
S
S
Gillies
A
A
D000319:Adrenergic beta-Antagonists / Q000009:adverse effects*; D000328:Adult; D001262:Atenolol / Q000009:adverse effects*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy; D017275:Isradipine / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D001620:beta-Thromboglobulin / Q000032:analysis
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D001620:beta-Thromboglobulin; D001262:Atenolol; D017275:Isradipine